The control of the production of the proteolytic enzyme plasminogen activator (PA) in normal human embryonic lung cells (HuEL) will be examined under in vitro tissue culture conditions and related to a pathological condition in vivo. Corticosteroids have been found to cause the reversible deinduction of PA in HuEL cells in vitro. Other agents or variables known to affect lung physiology, such as insulin or pH and O2 tension, will be examined with respect to their ability to affect PA levels in HuEL cells. The biosynthetic requirements for PA deinduction and induction will be explored by the use of antibiotics specific for the inhibition of unique classes of macromolecules. The role of intracellular protease inhibitors in regulating PA expression will also be determined. The regulation of PA production in HuEL cells in vitro will then be related to the possible abnormal production of PA in the lungs of individuals with Respiratory Distress Syndrome (RDS). The relationship between factors in vivo which predispose an infant to this disease will be compared to those factors in vitro which regulate PA production in HuEL cells. The plasma and sera of control and RDS infants will be analyzed for PA levels. In addition the PA produced by HuEL cells will be purified and antibodies produced against this enzyme will be used in an indirect fluorescent technique to determine if abnormally high levels of PA can be detected in RDS lungs. The ability to modulate PA production in a specific type of lung cell in vitro affords a unique opportunity both to determine those mechanisms controlling the synthesis of this enzyme and to assess the role of PA in the pathology of RDS.